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EXERTIONAL (EXERCISE-INDUCED) RHABDOMYOLYSIS

Rider, Brian C., Ph.D.; Coughlin, Adam M., Ph.D.; Carlson, Chad, Ph.D.; Hew-Butler, Tamara, DPM, Ph.D., FACSM

ACSM's Health & Fitness Journal: May/June 2019 - Volume 23 - Issue 3 - p 16–20
doi: 10.1249/FIT.0000000000000478
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Apply It! Gain a better understanding of exertional rhabdomyolysis (ER).

Understand how ER can affect your clients/athletes, how to identify the signs and symptoms, and most importantly, learn how you can work to prevent it from developing.

Brian C. Rider, Ph.D., CSCS,is an assistant professor of Kinesiology at Hope College. His research focuses on activity trackers and perceptual responses to exercise and physical activity.

Adam M. Coughlin, Ph.D.,is a professor of Kinesiology at the Saginaw Valley State University and investigates athlete performance and training volumes using intelligent, wearable technology.

Chad Carlson, Ph.D.,is an associate professor of Kinesiology and the Director of General Education at Hope College. His research occurs within the areas of sociocultural aspects of sport and physical activity.

Tamara Hew-Butler, DPM, Ph.D., FACSM,is an associate professor of Exercise Science at the Wayne State University. Her expertise is in exercise-associated hyponatremia and the endocrine regulation of fluid balance during exercise.

Disclosure: The authors declare no conflict of interest and do not have any financial disclosures.

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INTRODUCTION

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Rhabdomyolysis is a term that has been appearing in the news lately (1,2). This condition, which can result from strenuous exercise, is defined as the breakdown of the skeletal muscle, which unleashes a variety of muscle cell elements into the blood stream (3). One potentially dangerous element that is released from broken muscle cells is a very large protein called myoglobin. Myoglobin release into the bloodstream may block the kidney tubule, if present in large amounts for excretion, or can be broken down by the kidney into toxic byproducts, which can damage the kidney itself. In combination, excess myoglobin can lead to acute kidney injury, and in the worst case scenario, kidney failure (3). If muscle damage is particularly profound, the affected muscle tissue can swell significantly, get trapped within the confines of the surrounding fascia, and cause muscle necrosis (death) from what is commonly referred to as “compartment syndrome.”

Of historical interest, some of the first reported cases of rhabdomyolysis were not associated with exercise at all but rather resulted from “crush” injuries. Crush injuries occur when an object causes constant compression on the body. These types of injuries happen during natural disasters, like earthquakes or during war, when people get trapped under falling debris. In fact, four reported deaths from kidney failure were the result of crush injuries sustained in the London Blitz during World War II (4). Today, rhabdomyolysis as a result of crush injuries is exceedingly rare. Instead, rhabdomyolysis often results from the acute muscle damage that develops during strenuous or unaccustomed exercise. This “exercise-induced” rhabdomyolysis (most commonly referred to as exertional rhabdomyolysis or ER) is what all strength and conditioning specialists, coaches, trainers, and athletes must be acutely aware of when preparing for or participating in sports.

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SYMPTOMS

Exertional rhabdomyolysis (ER) is characterized by a breakdown of skeletal muscle at both an abnormal rate and volume (5). The first warning signs of ER are muscle swelling and prolonged and/or extreme muscle soreness beyond what one would normally expect, based on the intensity or duration of the exercise bout. The quickest and most accessible method of screening for ER is via urinalysis. Excess myoglobin leaked into the bloodstream will likely cause the athlete’s urine to be scanty, appear dark brown (sometimes referred to as “Coca-Cola” urine), contain elevated protein and blood, and have a pungent aroma (3). The definitive biomarker for diagnosis of ER is a blood test assessing levels of circulating creatine phosphokinase (CPK). CPK is a stable, nontoxic, cytosolic enzyme assumed to be present in “equal” amounts as myoglobin within the muscle cells. Because the half-life of myoglobin is short, clinicians and scientists often use CPK as a surrogate marker of myoglobin. Thus, CPK levels in excess of 10,000 U/L are generally thought to be a threshold for diagnosing clinically significant ER (6).

However, it is important to remember that a diagnosis of clinically significant ER requires not only elevated CPK levels (>10,000 I/U) but also a specific cluster of signs and symptoms that athletes, trainers, and coaches must be aware of. These signs and symptoms include the following:

  • muscle swelling (nonpitting edema),
  • soreness beyond what is expected for the exercise activity,
  • nausea with or without vomiting, and
  • dark brown or no urine produced.

Thus, clinically significant ER is only diagnosed when a combination of elevated CPK levels (>10,000 I/U) plus signs and symptoms of pathologic muscle damage are present together.

These signs and symptoms also fall along a continuum of transient and benign muscle soreness to life-threatening ER. For example, soreness after an exercise bout is one of the symptoms of ER, and yet when an individual engages in vigorous exercise, soreness is the body’s natural response. Oftentimes this soreness will persist for multiple days after the exercise session. This lingering soreness is commonly referred to as delayed onset muscle soreness and is a perfectly healthy and normal part of the muscle building and repair process. During dynamic (isotonic) activities, the muscle fibers will tear, signaling a multitude of body responses to begin repairing the damaged tissue. This process ultimately results in muscle growth (hypertrophy) and is responsible for the athlete’s strength gains. Seeing as this tear/repair process causes muscle soreness, this sensation, in and of itself, is not indicative of ER. Similarly, dark brown urine (another symptom of ER) without the accompanying soreness would not necessarily indicate an ER diagnosis. Urine color is influenced by a variety of factors, such as hydration status and nutritional intake. Although ER cases are exceedingly rare (a 2014 study (7) estimates the rate of incidence at 29.9 per 100,000 patient years), being aware of the signs and symptoms is critical for making sure that adequate medical assistance is provided when necessary.

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CAUSES

There are primary (exercise) and secondary factors that contribute to the development of ER. Reported incidents of ER are common in the weightlifting literature and among athletes competing in explosive anaerobic activities (3). The primary factors that could result in the development of ER after strenuous exercise are (a) the training status of the athletes and/or how acclimated they are to the exercise and (b) the intensity, duration, and type of exercise.

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Training Status/Acclimation

Although incidents of ER among sedentary nonathletes do occur (more on that later), these cases also develop in trained athletes who are performing unaccustomed exercise or high-intensity/volume exercise after a period of deconditioning (3,6). A recent article by Randy Eichner, M.D., FACSM, in ACSM's Current Sports Medicine Reports highlights these types of cases in collegiate and high school athletes across various sports, ranging from football to golf (1). The connecting thread in these reports was that ER occurred either after intense workouts that took place after an extended break (during the offseason), when the workout was novel to the athletes, or a combination of both. An aggressive workout easily handled by a conditioned person could prove too much in the same person during a period of deconditioning. Essentially, the workouts in all of these cases were, to quote Dr. Eichner, “too much, too soon, too fast” (1).

Thus, as with athletes, individuals who are new to exercise or returning to it after a prolonged absence should exercise extreme caution and restraint at the beginning. A prime example of deconditioned persons developing ER after an intense introduction/return to exercise can be found in U.S. military members. A 2017 report by Hill et al. (8) listed length of service as one of the key risk factors of army recruits developing ER. Specifically, those who were within the first 0 to 90 days of their service (i.e., during boot camp) were at an increased risk of ER. This risk extends to civilian nonathletes, where we are beginning to see an increasing number of ER cases resulting from high-intensity interval training (HIIT) activities. For example, a 2016 review by Cutler et al. (9) reported 29 incidents of ER that developed after a spin class. This news is especially concerning considering the increasing popularity of high-intensity exercise among nonathletes. In fact, the 2018 ACSM’s Worldwide Survey of Fitness Trends recently reported that HITT is the number one trend reported by fitness professionals (10). As the number of people participating in HITT-style workouts increases, so too should education of fitness professionals on the dangers of ER.

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Intensity/Duration/Type

Prolonged bouts of dynamic exercise can result in ER independent of a person’s training status. Previous literature reports various cases of marathoners, ultramarathoners, and even mountain bikers developing ER after long-distance events (11). Although long durations of exercise can elicit muscle damage sufficient to cause ER, other shorter, though no less strenuous, modes of exercise also can result in sufficient muscle damage. For example, in Kim et al.’s 2016 review (6), the authors noted more than 50% of the reported cases of ER occurred after weight training sessions. ER as the result of lower extremity exercise generally occurs after significant stress (1) (massive amounts of squats) or distance (11) (ultramarathoners), whereas upper extremity ER can occur with intense unaccustomed exercise of short (10 to 20 minutes) of exertion (12).

Muscle contraction type also is an important factor when determining the risk of ER. Exercises that involve a heavily eccentric muscle contraction predispose one to ER. The same 2016 review by Kim et al. (6) noted that a majority of reported ER cases occurred after an exercise primarily eccentric in nature. It should be noted that most often, dynamic exercise is a combination of both eccentric and concentric contractions, so it can be difficult to isolate the two. Dynamic muscle contractions (specifically eccentric) cause the muscles to tear, which then lead to the subsequent strength gains and muscle hypertrophy. However, although much is known about the impact of dynamic resistance training on muscles, much less is understood about the impact of static (isometric) exercise. Examples of static exercises are wall sits and planks, exercises often used by a personal trainer/strength coaches to supplement a workout. Although these activities often make up a small percentage of a resistance program, they are a useful tool in developing strength and stability. And, because there is muscle contraction involved but no change in length (eccentric or concentric) and thus less tearing due to contraction, it is worth understanding whether these types of exercise elicit muscle damage and if so to what degree.

Muscle contraction type also is an important factor when determining the risk of ER. Exercises that involve a heavily eccentric muscle contraction predispose one to ER.

Although there is little literature on its impact, a recent study presented at the 2017 ACSM Annual Meeting examined the muscle damage associated with an “endurance” tug-of-war (13). This tug-of-war placed great strain on the musculoskeletal system and lasted for almost 3 hours. However, this strain was largely isometric in nature. Participants spent the majority of the event stationary, horizontal, at the ground level, with the rope secured against their body and their legs locked out (see Figure 1). Because of its duration and intensity, there is reason to suspect that despite the lack of eccentric contractions, significant levels of muscle damage occurred. Thus, this event offered investigators a unique opportunity to investigate the impact prolonged isometric activity has on the musculoskeletal system.

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Secondary Factors

Secondary factors that can exacerbate the degree of skeletal muscle breakdown include the following: (a) hot environments, (b) nutrition, (c) sex, and (d) workout supplements/alcohol (6). Exercising in high temperatures and humidity has been linked to cases of ER. This has been seen most often in the literature on soldiers during specialized training in the heat. In addition, low-protein or high-protein intake may be associated with ER, according to a reported incident of a vegetarian athlete whose diet was protein deficient, leading to an exacerbated case of ER (14) after exercise, or by athletes ingesting protein shakes in another study (12). ER also disproportionally affects males, although the mechanisms as to why remains unclear. Finally, supplements (such as creatine) and alcohol can both result in imbalances within the body. Both dehydration and overhydration have been shown to augment skeletal muscle breakdown or contribute to more dire consequences. Secondary factors do not necessarily predispose an individual to ER but may exacerbate or prime skeletal tissue for enhanced breakdown from biochemical processes, which destabilize the skeletal muscle cell membrane.

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CONSEQUENCES (ACUTE AND CHRONIC)

ER is a consequence of exercise with possible outcomes that range from lingering but transient soreness to kidney failure, disability (compartment syndrome with fasciotomy, i.e., cutting of the fascia to relieve pressure), and even death. However, the good news is that these more severe consequences are exceedingly rare, especially if an athlete seeks treatment in a timely manner. Current literature suggests that if treated, there seem to be no long-lasting health complications associated with ER. Thus, it’s all the more important that coaches and trainers, along with the athletes themselves, are well versed in the signs and symptoms of ER.

ER is a consequence of exercise with possible outcomes that range from lingering but transient soreness to kidney failure, disability (compartment syndrome with fasciotomy, i.e., cutting of the fascia to relive pressure), and even death. However, the good news is that these more severe consequences are exceedingly rare, especially if an athlete seeks treatment in a timely manner.

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IN SUMMARY

Although rare in occurrence, ER is still a concern for athletes. Care providers/coaches should recognize the increased risk of ER when instituting new and/or aggressive dynamic exercise routines, regardless of training status but especially among lesser-trained individuals.

Although rare in occurrence, ER is still a concern for athletes. Care providers/coaches should recognize the increased risk of ER when instituting new and/or aggressive dynamic exercise routines, regardless of training status but especially among lesser-trained individuals.

Simply put: monitor your athletes! Understand that they are arriving, especially preseason, with different training backgrounds and experiences, and that everyone might not be able to handle the same stress and training load right away. Workouts should be individualized to the best of a strength coach’s capabilities. In addition, do not disregard players’ reports of prolonged, lingering soreness especially 24 to 48 hours after a training session. Trainers working with nonathletes should exercise caution and restraint, not allowing previously sedentary individuals to jump into high-intensity exercise without first an appropriate acclimation period.

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SIDE BAR

Each Fall, Hope College (Holland, MI) hosts a unique tug-of-war, known as “The Pull” between members of the freshman and sophomore classes. The Pull uses two, 18-person teams where pullers recline in pits they have dug into the ground and wrap the rope around themselves. Whereas a modern tug-of-war is anaerobic in nature, The Pull is an endurance tug-of-war in which the athletes rely on sustained isometric contractions for up to 3 hours. The Pull is a tug-of-war of attrition, in that the team that fatigues the least ultimately prevails. Participating in this type of activity for hours on end places great strain on the musculoskeletal system.

The unique nature of The Pull makes it difficult to compare it to other sports/competitions. However, our data seem to indicate that isometric exercise elicits muscle damage outside of normal resting values (0–300 U/L) that is in line with research from other sports/exercises (15,16). However, these elevated values do not approach the levels of clinical rhabdomyolysis (>10,000 U/L) nor are they associated with any electrolyte or renal function derangements. For comparison, a study by Mougios et al. (16) examined CPK levels across a wide range of athletes and nonathletes to establish CPK reference intervals. The authors found that soccer and swimming values for males were between 83 to 1,492 U/L and 70 to 523 U/L, respectively. The participants' CPK values after the tug-of-war were 1,384.8 ± 936.6 U/L. These results aid in our understanding of the effect that isometric muscle contraction has on muscle damage. It seems that an endurance tug-of-war elicits transient (nonclinically significant) muscle damage, similar to other sports in its physiological impact on the body.

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BRIDGING THE GAP

ER is a serious medical condition that can affect athletes and nonathletes alike. Although rare in its occurrence, it is important that strength coaches and trainers understand the underlying causes, so they can protect their athletes/clients. Specifically, to the best of their ability, they should individualize workouts and understand each person's exercise history and current training status. In addition, they should exercise caution when introducing novel forms of exercise that an individual will be unaccustomed to.

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References

1. Eichner ER. Football team rhabdomyolysis: the pain beats the gain and the coach is to blame. Curr Sports Med Rep. 2018;17:142–3.
2. Eichner ER. Exertional rhabdomyolysis stays in the news. Curr Sports Med Rep. 2016;15:378–9.
3. Kahn F. Rhabdomyolysis: a review of the literature. Neth J Med. 2009;67:272–83.
4. Bywaters EG, Beall D. Crush injuries with impairment of renal function. Br Med J. 1941;1:427–32.
5. Baird M, Graham S, Baker J, Bickerstaff G. Creatine-kinase- and exercise-related muscle damage implications for muscle performance and recovery. J Nutr Metab. 2012;2012:960363.
6. Kim J, Lee J, Kim S, Ryu Young H, Cha SK, Sung DJ. Exercise-induced rhabdomyolysis mechanisms and prevention: a literature review. J Sport Health Sci. 2016;5:324–33.
7. Tietze DC, Borchers J. Exertional rhabdomyolysis in the athlete: a clinical review. Sports Health. 2014;6(4):336–9.
8. Hill O, Scofield D, Usedom J, et al. Risk factors for rhabdomyolysis in the U.S. Army. Mil Med. 2017;182:1836–41.
9. Cutler T, DeFilippis E, Unterbrink M, Evans A. Increasing incidence and unique clinical characteristics of spinning-induced rhabdomyolysis. Clin J Sport Med. 2016;26:429–31.
10. Thompson WR. Worldwide survey of fitness trends for 2018. ACSMs Health Fit J. 2017;21:10–9.
11. Chlibkova D, Knechtle B, Rosemann T, et al. Rhabdomyolysis and exercise-associated hyponatremia in ultra-bikers and ultra-runners. J Int Soc Sports Nutr. 2015;12:29.
12. Stanfa MR, Silles NN, Cooper AB, et al. Risk factors for collegiate swimmers hospitalized with exertional rhabdomyolysis. Clin J Sport Med. 2017;27:37–45.
13. Rider BC, Coughlin AM, Carlson C, et al. The strain of The Pull: examining the physiological effects of an endurance tug-of-war. Med Sci Sport Exerc. 2017;49:462.
14. Borrione P, Spaccamiglio A, Salvo RA, Mastrone A, Fagnani F, Pigozzi F. Rhabdomyolysis in a young vegetarian athlete. Am J Phys Med Rehabil. 2009;88:951–4.
15. Fallon KE, Sivyer G, Sivyer K, Dare A. The biochemistry of runners in a 1600 km ultramarathon. Br J Sports Med. 1999;33:264–9.
16. Mougios V. Reference intervals for serum creatine kinase in athletes. Br J Sports Med. 2007;41:674–8.
Keywords:

Rhabdomyolysis; Creatine Kinase; Muscle; Exercise

© 2019 American College of Sports Medicine.